Background

Historically, 5-year survival rates in patients with locally advanced pancreatic cancer have been dismal (<10%), even following a Whipple resection. Disease recurrence is typically both local and distant. Further advances in the management of pancreatic cancer led to the incorporation of chemotherapy and radiotherapy following surgery, with a subsequent improvement in 2-year survival from 18% to 43% according to the GITSG studies. In 2000, Nukui et al reported the results of a phase II study using more aggressive chemoradiation in addition to interferon for the treatment of locally advanced pancreatic cancer. The study employed continuous infusion 5-FU, weekly cisplatin, and subcutaneous interferon concurrent with radiation in the post-operative setting. The rationale for interferon was possible enhancement of tumoricidal effects of certain chemotherapeutic agents. The authors reported a 2-year survival rate of 84% with this aggressive treatment approach. This current article by Picozzi et al serves as an update to the results reported by Nukui et al in 2000.

Materials and Methods

A cohort of 43 patients were evaluated, all with ductal adenocarcinoma of the pancreatic head and of pancreatic origin

Primary tumors of the distal common bile duct, ampulla, and duodenum were excluded

All patients underwent pancreaticoduodenal resection (Whipple)

Approximately 6-8 weeks following resection, patients were begun on concurrent chemo-radiation as well as interferon therapy

Follow-up was obtained by telephone contact, and evidence of relapse was determined by physical examination, CXR, and CT scans

Statistical evaluation was done using Kaplan-Meier analysis

Results

Between 1995-2002, 43 patients were accrued, with a median patient age of 62 years

Median patient follow-up was 21.8 months (range of 4-86 months)

All but 7% of patients had pylorus-preserving surgery, and 2 had total pancreatectomies

Two percent of patients had stage I disease, 12% had stage II, 72% had stage III, and 14% had stage IVa disease

Eighty-four percent of patients had positive lymph nodes with an average of 2.2 nodes per patient

With regard to histology, 26% were poorly differentiated, and there was perineural invasion in 68% of samples

A total of 19% patients had gross or microscopic positive margins

Ninety-five percent of patients completed their radiation course

Ninety-three percent of patients received greater than 85% of the intended 5-FU dose, while the last dose of cisplatin was held in 28% of patients

With regard to adjuvant chemotherapy, 56% of patients got 100% of the intended 5-FU dose, and 70% received >85% of the intended dose

Treatment-related toxicity was mostly gastrointestinal, with grade 3 toxicity in 70% of the patients; 70% had some form of delay in their chemoradiotherapy, while 43% of patients were hospitalized for treatment-related toxicity

Actuarial overall survival at 1, 2, and 5 years was 95%, 64%, and 55% respectively; disease-free survival was 67%, 52%, and 52% at 1, 2, and, 5 years respectively

Discussion

When compared to other studies using adjuvant chemotherapy, the results of this study demonstrate the highest survival rates to date, and thus are very encouraging

However, this improvement in survival comes at the cost of significantly increased treatment-related toxicity requiring hospitalization in 42% of patients

Though toxicity was high, there was no treatment-related mortality

There was no mention of the performance status of enrolled patients, but one should assume that patients were carefully selected for this aggressive treatment regimen

All surgeries were performed at a single institution with one surgeon performing 91% of the resections; it will be interesting to see if the same results will hold when surgery is performed at other centers.